Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model.
We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ras mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs.
Yoshidome
K
K
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Shibata
M A
MA
Maroulakou
I G
IG
Liu
M L
ML
Jorcyk
C L
CL
Gold
L G
LG
Welch
V N
VN
Green
J E
JE
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics*; D051381:Rats